Method and apparatus for supplying gas to an area

ABSTRACT

An apparatus for supplying one or more gases, such as oxygen, to a target area, comprising a top layer and a bottom layer sealed around the perimeter of the layers to form a reservoir between the layers, wherein the top layer is not gas-permeable and the bottom layer is highly gas-permeable, said reservoir containing one or more gases. The present invention also describes methods of using such an apparatus to supply oxygen to a wound for improved wound healing.

This application claims the benefit of U.S. Application Ser. No.60/479,745, filed on Jun. 18, 2003, which is herein incorporated byreference in its entirety.

FIELD OF THE INVENTION

The present invention relates generally to supplying a gas to an area.

BACKGROUND OF THE INVENTION

Throughout this application various publications are referenced byarabic numerals within parentheses. Full citations for thesepublications may be found at the end of the specification immediatelypreceding the claims. The disclosures of these publications in theirentireties are hereby incorporated by reference into this application inorder to more fully describe the state of the art to which thisinvention pertains.

The healing of wounds and the effect of oxygen tension has beenintensively studied (1). Among the components important in the healingprocess are fibroblast proliferation, angiogenesis, collagen synthesis,and reepithelialization.

Soon after injury, whether accidental or surgically induced,undifferentiated mesenchymal cells transform to migratory fibroblasts,which migrate into and across the injured wound. It is known thatfibroblasts are aerobic in nature. Fibroblasts are stimulated to producecollagen. While experiments from cultured fibroblasts suggest that highlactate and ascorbic acid concentration typical of hypoxic conditionsmay activate some of the fibroblast collagen-synthesizing enzymes,animal studies involving low, normal, and high oxygen tensionsnevertheless demonstrate increased rates of collagen synthesis underhyperoxic rather than hypoxic conditions.

Angiogenesis, on the other hand, appears to be stimulated by a hypoxictissue gradient, with new capillaries extending in the direction oflower oxygen concentration. When a hypoxic gradient no longer exists,angiogenesis is minimized or static. Epithelialization is also known tobe related to oxygen tension, with higher rates of epithelialproliferation observed under hyperoxic as opposed to hypoxic conditions.

The supply of oxygen to healing wound tissue may be derived from threesources: oxygen chemically bound to hemoglobin in whole blood; oxygendissolved in plasma; and oxygen which diffuses into plasma or tissuefrom the exterior. In deep wounds, the latter is of little importance.The studies of R. P. Gruber et al., for example, indicate that oxygentension, measured polarographically, increases markedly at 3 bar of 100%O₂ in the superficial dermis (0.30-0.34 mm), while the relative oxygenconcentration of the deep dermis (1.8-2.2 mm) is unchanged under thesame conditions (2).

In surface wounds, all sources of oxygen are important. In wounds oflarge surface area, however, for example ulcers, only the tissue at theedges of the ulcer or at its base are well supplied with blood, and thegrowing granulation tissue, in the absence of oxygen diffusing from theexterior, must be supplied by diffusion from blood vessels and plasma, arelatively inefficient process.

It is well established, also, that occlusive coverings that maintain amoist environment promote wound healing (3). Furthermore, it is wellknown that the changing of wound dressings may interfere with thehealing process by disrupting the healing tissue where granulation andcollagen synthesis has not imparted sufficient tensile strength to avoidrupture upon dressing removal. However, due to the inability of theblood and plasma to supply optimal oxygen concentration, and due to thefurther reduction in oxygen from the exterior brought about by thepresence of the occluding dressing, a hypoxic condition may rapidly bereached. Although this condition may encourage angiogenesis, itnegatively affects collagen synthesis and epithelialization. Moreover,various clostridium species, e.g., C. perfringens and C. septicum, areinduced to germinate under hypoxic conditions, which can also supportother anaerobic flora (4). In addition to minimizing anaerobic flora bydiscouraging germination, hyperoxic conditions are known to reduce theconcentration of other pathogens as well.

Past treatment of chronic ulcers and gangrenous tissue has, in manycases, involved extensive debridement in combination with antibioticsand systemic hyperbaric oxygen. Room size hyperbaric oxygen chambers orchambers sized for the individual patient have employed pure oxygen atpressures of 2 to 3 bar. Treatment time is limited, as oxygen toxicityand central nervous system (CNS) disorders may result from the increasedoxygen content of the blood. Such treatments have met with a great dealof success, but the success may not be due to the increased systemicblood and plasma-derived oxygen supply. The blood and plasma alreadycontain sufficient oxygen for the healing process. Rather, it is thediffusion-limited access of oxygen to the wound that limits the oxygensupply required for optimal healing and minimization of infection. Theincreased oxygen tension in the wound most likely results directly fromincreased diffusion into the wound surface from the oxygen in thechamber. Gruber, for example, indicates that rate of oxygen absorptionfrom the skin is roughly proportional to oxygen concentration fromnearly 0% to 30% (2). Gruber further indicates, however, that oxygenabsorption tends to level off at higher oxygen concentrations.

Due to the expense of large hyperbaric chambers and the systemic effectsof oxygen toxicity that they may engender, topical hyperbaric chambershave been proposed. Topical chambers operating at “normal” hyperbaricpressures of 2-3 bar are difficult to seal to the body or extremitybeing treated, however, without interfering with blood supply to thewound locus. Thus, hyperbaric chambers operating at only modestlyelevated pressure have been manufactured, such as a device operating at22 mm Hg pure oxygen (1.03 bar) (5). However, such chambers areexpensive and difficult to sterilize (6). Cross-infection is stated tobe common.

Heng and others have proposed a simple hyperbaric oxygen treatmentchamber consisting of a polyethylene bag that may be secured to the bodyor extremity with adhesive tape (6), or a transparent nylon bag withstraps and VELCRO® closures (7). Pressure is maintained at between 20 mmHg and 30 mm Hg. However, the leakage associated with the sealing ofsuch bags requires a relatively high rate of oxygen flow. Thus, thismethod is useful only in facilities with sufficient oxygen supply, or incontrolled home environments where a large oxygen tank is permissible. Adisposable hyperbaric treatment bag with improved closure is disclosedin U.S. Pat. No. 5,029,579. Another disposable hyperbaric treatment bagis disclosed in U.S. Pat. No. 5,478,310.

In U.S. Pat. No. 4,875,483, a combination layered dressing having anexternal low oxygen-permeability layer and an abutting internal oxygenpermeable layer has been proposed. The relatively low permeabilityexterior layer is left attached for 3 to 72 hours creating hypoxia, andhopefully stimulating angiogenesis, following which this layer isremoved. However, although the remaining, and now exterior layer isoxygen permeable, the layer nevertheless decreases oxygen transport, andthus hyperbaric treatment, by one of the methods previously described,may be necessary to elevate oxygen levels sufficiently to provideoptimal healing.

Ischemia compromises wound healing and wounds in aging populations aremore ischemic than those in younger populations (8). It has beendemonstrated in ischemic rabbit ear models that topical or hyperbaricoxygen can convert a non-healing wound into a healing wound, and thatgrowth factors (PDGF) provide a synergistic benefit when used withoxygen (9).

It is well known that the speed of epidermal migration on the normalwound is critically dependent on the amount of oxygen available, andthis is the rate-limiting step. The control of the local environment isdependent on the local blood supply and the diffusion of oxygen from theatmosphere. Any form of treatment that encourages an increase in thewound fluid and reduces the time during which the wound is non-perfusedwill tend to increase the rate of healing (10, 11).

It is generally agreed that the tissue surrounding a wound does notalone supply sufficient oxygen for wound repair, and that atmosphericoxygen is required for the formation of hydroxyproline, a key element inepidermal wound healing. It has been demonstrated that 93% of the oxygenincorporated into the hydroxyl groups of newly synthesizedhydroxyproline is derived from the atmosphere (12).

It is further generally known that it is likely that oxygen reaches theepidermal cells directly by diffusion through the scab rather than viathe vascular or tissue supply. Prior studies of wounds covered withplastic films found that the higher the oxygen permeability of the film,the greater the healing rate (13, 14). Furthermore, the films preventedscab formation, thereby altering the mode of epidermal regeneration. Theuse of wound dressings that prevent scab formation and have increasedoxygen permeability are thought to improve wound healing. The increasedpresence of oxygen speeds the re-establishment of epithelial continuity.Direct access of pure oxygen to open wounds promotes epidermal cellmigration.

Kaufman et al. showed a continuum in wound healing improvement whenchanging humidified oxygen levels from 21 to 60, and 80-96% on fullthickness burns on guinea pigs (15). Niinikoski also suggested thatcollagen accumulation in the dead space of animal wounds increases withoxygen concentration of the environment, peaking at 70% (16).

A review of topical oxygen and bum wound healing states that oxygen isessential for the contraction, the dominant healing process (17).Topical oxygen has also been shown to improve the healing rate of skinulcers and wounds where an inadequate supply of oxygen results fromperipheral vascular disease or local injury to the microcirculation.Fischer showed topical hyperbaric oxygen treatment improvedepithelialization and contraction of decubitus ulcers (5).

Utkina demonstrated that moderate increases in oxygen levels at normalatmospheric pressure increases the closure rate of open wounds (18). Heshowed healing rate improved with continuous exposure to 45%.

A number of patents have been issued that disclose the use of localgeneration of oxygen at the wound site to treat wounds in bandagesystems using chemical reactions, oxygen saturated solutions, orelectrochemical generators (see U.S. Pat. Nos. 5,855,570, 5,578,022,5,788,682, 5,792,090 and 6,000,403). These concepts have not beencommercialized. The present invention allows for gas to be containedsimply into the wound dressing, which creates a wound environment withcontinuous exposure to preset oxygen levels, without need for a gassource such as a generator, saturated solution or a chemical reaction.Since the amount of oxygen consumed by metabolic processes in the woundis relatively small, the materials for the dressing and the volume ofthe oxygen cavity in the dressing can be selected to maintain thedesired oxygen concentration for the practical life of the dressing

Prior to this invention, larger amounts of oxygen were believed to berequired to benefit wound healing, which justified the need for anoxygen releasing source However, the actual amount of oxygen that thewound consumes in cell metabolism is quite small, and simply requires adesign that assures a large diffusion gradient for oxygen into the woundduring the healing period. Hyperbaric approaches that use elevatedpressure to further enhance the oxygen diffusion gradients to transfermore oxygen into the tissue are only used briefly, and once the patientis withdrawn from the high-pressure environment, the oxygen levels inthe wound drop down to pre-exposure limits quickly. The presentinvention operates as a hyperoxic environment without the need for usingelevated pressure to create the oxygen diffusion gradient.

Supplying oxygen to a wound on a continuous and ambulatory basis is ofbenefit to speed healing and reduce infection. The oxygen dressingdescribed below can be complimentary to other therapies and can addressa rate-limiting step for various types of wounds.

SUMMARY OF THE INVENTION

The present invention is an apparatus that is capable of providing oneor more gases to a target area. One embodiment of the invention is amulti-layer wound dressing comes pre-filled with high levels of oxygenbetween the layers. The top layer is a barrier film that holds theoxygen over the wound, while the bottom layer is a high transfer ratefilm, attached over the wound. This self-contained dressing is appliedto the wound like conventional wound dressings, and can be manufacturedwith a similar size, weight and feel of conventional dressings ortransdermal patches.

The barrier layer holds the oxygen in the vicinity of the wound, whilethe permeable or porous layer allows the oxygen to diffuse into thewound fluid at a rate proportional the gradient, until the wound fluidis saturated. The dressing acts like an oxygen reservoir, and as oxygenis consumed by the wound, there is a local abundant supply to be used asneeded.

While oxygen is a rate-limiting component in the wound healing process,the oxygen transfer across intact skin is insignificant, and oxygenconsumption by a wound is a relatively small number, estimated to be10⁻⁴ cc/mL fluid-hr. Therefore the design of the dressing is influencedmost significantly by the diffusion rates of the relevant gases throughthe barrier material, the target gas concentration range on the patient,the length of time the dressing may be worn, and the seal integrity ofthe dressing to itself and to the patient

The dressing would be removed by the user from a package that usescontrolled atmospheric packaging (CAP) to maintain the productintegrity. CAP is specifically a package with high barrier propertiesthat contains the desired ratio of gases to preserve the product. CAP iswell known in the food industry and examples of the types of CAP thatmay be used are described in U.S. Pat. No. 4,895,729 and in thepublished literature (19, 20, 21, 22, 23).

The dressing will accelerate healing of acute and chronic wounds, aswell as provide antibacterial and antifungal benefits.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate one embodiment of the inventionand, together with the description, explain one embodiment of theinvention. In the drawings,

FIG. 1 illustrates one embodiment of a dressing system.

FIG. 2 illustrates one embodiment of a packaging system.

FIG. 3 illustrates one embodiment of a gas emitting pouch system.

FIG. 4 illustrates a flow diagram for utilizing a packaging systemaccording to one embodiment of the invention.

FIG. 5 illustrates a flow diagram for utilizing a dressing systemaccording to one embodiment of the invention.

FIG. 6 illustrates one embodiment of a pouch system.

DETAILED DESCRIPTION

The following detailed description of the invention refers to theaccompanying drawings. The detailed description merely providesexemplary embodiment of the invention and is not intended to limit theinvention.

FIG. 1 illustrates an apparatus for supplying one or more gases, alsoreferred to herein as a dressing system 100. The dressing system 100 isshown as an exemplary perspective cut-away view to more clearlyillustrate the invention. In one embodiment, the dressing system 100 isconfigured to contain a gas that is dispensed to a user wearing thedressing system 100. For example, the different gases contained withinthe dressing system 100 may include but is not limited to oxygen, carbondioxide, and/or nitrogen.

As used herein, the term “gas” includes any gas or volatile.

The dressing system 100 includes a seal 110, an external barrier (or toplayer) 120, a reservoir 130, an absorbent ring 140, an adhesive backing150, a permeable film (or bottom layer) 160, and a compliant porousinsert 170.

The seal 110 is configured to bond the external barrier 120 and thepermeable film 160 together such that the reservoir 130 is formed.

The external barrier 120 is selected to be non-permeable to gases. Forexample, the external barrier 120 may be constructed of metallizedpolyester, ceramic coated polyester, polyvinylidene chloride laminatessuch as Saranex®, EVOH laminates such as Oxyshield®, or polyamidelaminates such as Capran®. In one embodiment, the external barrier 120may be configured to conduct heat or electrical stimulation from anexternal source to the user. For example, polyethylene or anotherinfrared transmittable material may be utilized as the external barrier120.

The permeable film 160 is configured to be permeable to gases. Forexample, the permeable film 160 may be constructed of polyurethane,silicone, polyvinylchloride, polyolefins, and the like, preferablyethylene vinyl alcohol (EVA) or EVA/polyethylene.

The reservoir 130 is configured to store a gas while the dressing system100 is worn by a user. In one embodiment, the stored gas within thereservoir 130 is controllably released to the user through the permeablefilm 160.

The amount of gas released to the user while wearing the dressing system100 may vary according to the concentration of the gas contained withinthe reservoir 130 and the material used as the permeable film 160. Otherfactors such as temperature and atmospheric pressure may also affect theamount of gas released to the user.

The absorbent ring 140 may be located adjacent to the permeable film 160and may be configured to wick away moisture from the user.

The adhesive backing 150 is configured to adhere the dressing system 100to the user. Further, the adhesive backing 150 may also be utilized toprevent the gas that is delivered through the permeable film 160 to theuser from escaping. In one embodiment, the adhesive backing 150 maycover the perimeter of the dressing system 100. In another embodiment,the adhesive backing may cover the entire dressing system 100 and may beintegrated with the permeable film 160.

Examples of the types of adhesive that may be used in the presentinvention are described in U.S. Pat. Nos. 6,284,941 and 5,308,887. Inone embodiment, the adhesive backing may be comprised of adhesive usedin commercially available adhesive bandages. In another embodiment, theadhesive backing may be comprised of a gel adhesive. The gel adhesivemay be comprised of a hydrogel. The gel adhesive may also be reusable,such that the dressing system could be removed from the user andreplaced more than once.

The compliant porous insert 170 is configured to prevent gas debt inareas caused by pressing the external barrier 120 directly on to thepermeable film 160. In one embodiment, the compliant porous insert 170placed within the reservoir 130 and between the external barrier 120 andthe permeable film 160.

The elements comprising the dressing system 100 are shown forillustrative purposes only. Deletion or substitution of any shownelements does not depart from the spirit and scope of the invention.Similarly, the addition of new elements does not depart from the spiritand scope of the invention.

In one embodiment, the dressing system 100 is configured to bepre-filled with high levels of oxygen within the reservoir 130. In thisembodiment, the dressing system 100 is configured to be placed over awound of the user to help the wound heal. In one embodiment, theexternal barrier 120 is configured to hold the oxygen within thedressing system 100 and the permeable film 160 is a high transfer ratefilm and is configured to provide oxygen over the wound. In other words,the external barrier 120 holds the oxygen in the vicinity of the wound,while the permeable film 160 allows the oxygen to diffuse into the woundfluid at a rate proportional the gradient, until the wound fluid issaturated.

Subsequent to the saturation, the dressing system 100 acts as an oxygenreservoir; as oxygen is consumed by the wound, there is a local abundantsupply of oxygen to be provided to the wound as needed.

The proportions of the dressing system 100 may be influenced by thediffusion rates of the relevant gases through the permeable film 160,the target gas concentration range on the user, the length of time thedressing system 100 may be worn, and the seal integrity between thedressing system 100 and the user. The dressing system 100 may acceleratehealing acute and chronic wounds, as well as provide antibacterial andantifungal benefits.

In another embodiment, in addition to providing gas to a user, thedressing system 100 may be configured to deliver biologically beneficialagents such as drugs, minerals, nutrition, amino acids, pH modifiers,anti-microbials, growth factors, enzymes to the user. In one embodiment,integrating the delivery systems of the gas with the beneficial agentadditives may lead to synergistic effects that are not achieved by justthe gas or the beneficial agent additives alone. In one embodiment,these biologically beneficial agents may be delivered asmicroencapsulated agents incorporated in the adhesive backing 150. Inanother embodiment, the microencapsulated agents may be available in agel matrix in the dressing cavity 180, accessible to the wound throughpores or perforations, or using conventional transdermal technologies.

In an alternate embodiment, instead of filling the reservoir 130 withgas, a substance is included within the reservoir 130 to generate gaswithin the reservoir 130. For example, oxygen-releasing agents may beincluded within the reservoir 130. Oxygen releasing agents includeoxygen releasing inorganic salts, hydrogen peroxide containingformulations, intercalated magnesium peroxide, sodium percarbonate,sodium carbonate and hydrogen peroxide, and the like.

In yet another embodiment, the permeable film 160 may be deleted and thecompliant porous insert 170 may be utilized to hold a substance forgenerating a gas within the dressing system 100.

In yet another embodiment, the external barrier 120 is comprised ofSaranex®, the permeable film 160 is a polyurethane high oxygenpermeability film, these two layers are hermetically sealed around theperimeter, and the reservoir 130 contains 98% oxygen. One method ofachieving the specified oxygen concentration in the reservoir 130 and tocreate the controlled atmospheric packaging is to (1) assemble dressing,sealing the reservoir with normal atmospheric conditions (about 21%oxygen); (2) place the dressing in the metallized film package; (3)flush the package with 100% oxygen; and (4) seal the package. Instorage, the gas in the reservoir 130 will come to equilibrium with thegas in the package via the permeable film 160. When the product isreceived by the customer and opened, the gas in the reservoir willachieve 98% oxygen. The materials and dimensions used are determined bytaking into account these objectives.

In another embodiment, the dressing system as described herein mayfurther comprise a septum, which is defined herein as a septum, a valve,a Luer-type fitting or any resealable opening through which one or moregases can be introduced into the dressing system, then resealed toprevent the one or more gases from escaping. The dressing system of thisembodiment may be applied to the wound, then the one or more gases inthe desired ratio may be introduced into the dressing system, e.g., witha syringe. The septum would also allow for refilling of the dressingsystem, if desired.

FIG. 2 illustrates a packaging system 100. The packaging system 100 isshown as an exemplary perspective cut-away view to more clearlyillustrate the invention. In one embodiment, the packaging system 200 isconfigured to contain a gas within an enclosed container 210, which iswithin the packaging system. For example, the different gases containedwithin the dressing system 100 may include but is not limited to oxygen,carbon dioxide, and/or nitrogen.

The enclosed container 210 is also configured to hold the dressingsystem 100 as shown and described corresponding to FIG. 1. Once theenclosed container 210 is sealed, the enclosed container issubstantially impermeable; the gas within the enclosed container 210substantially remains within the enclosed container 210. Further, theenclosed container 210 utilizes controlled atmospheric packaging (CAP)to maintain the environment within the enclosed container 210. In oneembodiment, CAP is a package with high barrier properties that containsthe desired ratio of gases to preserve the internal environment.

The gas within the enclosed container 210 may permeate the dressingsystem 100 through the permeable film 160.

In one embodiment, the packaging system 200 may be utilized to store thedressing system 100 without degrading the gas stored within thereservoir 130 within the dressing system 100 when the gas within thereservoir 130 and the gas within the enclosed container 210 are thesame.

In another embodiment, the packaging system 200 may be utilized tochange the concentrations of gases in the dressing system 100. The gasconstituents stored within the enclosed container 210, diffuse into thedressing system 100 when the concentration of the gas within thecontainer 210 is higher in concentration compared to the gas within thedressing system 1 00. Similarly, the gas constituents stored within thedressing system 100, diffuse into the container 210 when theconcentration of the gas within the container 210 is lower inconcentration compared to the gas within the dressing system 100. Thegases may diffuse through the permeable film 160 until the constituentsreach equilibrium, the same concentrations on both sides of thepermeable film.

FIG. 3 illustrates a gas emitting pouch system 300. The gas emittingpouch system 300 is shown as an exemplary perspective cut-away view tomore clearly illustrate the invention. In one embodiment, the gasemitting pouch system 300 is configured to contain a gas that isdispensed to the local area surrounding the gas emitting pouch system300. For example, the different gases contained within the gas emittingpouch system 300 may include but is not limited to oxygen, carbondioxide, and/or nitrogen.

The gas emitting pouch system 300 includes a first permeable film 310, asecond permeable film 320, and a reservoir 330.

In one embodiment, the first permeable film 310 is coupled with thesecond permeable film 320 and forms the reservoir 330 for storing gaswithin the gas emitting pouch system 300. For example, the first andsecond permeable films 310 and 330 may be constructed of polyurethane,polyethylene, silicone films, polyvinylchloride, and the like.

The reservoir 330 is configured to store a gas while the gas emittingpouch system 300 is being used. In one embodiment, the stored gas withinthe reservoir 330 is controllably released to the area surrounding thegas emitting pouch system 300 through the first and second permeablefilms 310 and 320.

The amount and rate of gas released through the gas emitting pouchsystem 300 may vary according to the concentration gradients of the gasacross the permeable films that comprise the walls of reservoir 330 andthe materials used as the first and second permeable films 310 and 320.310 and 320 can be the same or different materials. The amount and rateof release of gas can be different on the opposite sides, this can occurwhen 310 and 320 have different permeabilities. Other factors such astemperature, humidity and atmospheric pressure may also affect theamount of gas released.

The elements comprising the gas emitting pouch system 300 are shown forillustrative purposes only. Deletion or substitution of any shownelements does not depart from the spirit and scope of the invention.Similarly, the addition of new elements does not depart from the spiritand scope of the invention.

In one embodiment, the gas emitting pouch system 300 is configuredprefilled with the desired gas concentrations and is stored within thepackaging system 200 (FIG. 2) prior to releasing gas into thesurrounding environment, also prefilled with the same gas concentrationsas in the gas emitting pouch, in order to maintain the levels in thepouch. In another embodiment, the gas within the reservoir 330 withinthe gas emitting pouch system 300 comes to equilibrium within thepackaging system 200 so that both the pouch and the package reach thetarget concentrations

In one embodiment, the gas emitting pouch system 300 is configured to beplaced in an environment where the gas stored within the reservoir 330is released steadily into the surrounding environment, as the gradientdoesn't change appreciably. In another embodiment, the release rate ofgas from the reservoir 330 into the surrounding environment slows as thesurrounding environment becomes saturated with the gas. Subsequent tothe saturation, the gas emitting pouch system 300 acts as a gasreservoir; as gas is dissipated from the surrounding environment, thereis a local supply of gas within the reservoir 330 to be provided to thesurrounding environment, governed by the transfer rate across thepermeable film.

The gas emitting pouch 300 has many applications which may includenon-medical applications such as applying the gas emitting pouch 300 toeffect environments in containers for any purpose such as labexperiments, food preservation, to accelerate degradation, to preventcorrosion, and the like.

The flow diagrams as depicted in FIGS. 4, and 5 illustrate merely oneembodiment of the invention. The flow diagrams in FIGS. 4 and 5 are oneparticular use of the invention based on a specific application. Inother embodiments, the invention may be utilized with otherapplications. The blocks within the flow diagrams may be performed in adifferent sequence without departing from the spirit of the invention.Further, blocks may be deleted, added, or combined within each of theflow diagrams without departing from the spirit of the invention.

The flow diagram in FIG. 4 illustrates an exemplary process of utilizingthe packaging system 200 according to one embodiment.

In Block 410, a gas-retaining object is placed within the packagingsystem 200. In one embodiment, the gas-retaining object is the dressingsystem 100. In another embodiment, the gas-retaining object is gasemitting pouch system 300. In yet another embodiment, the gas-retainingobject may be any item that is configured to retain and controllablyrelease a gas from the object.

In Block 420, the packaging system 200 is flushed with a gas. In oneembodiment, the packaging system 200 is flushed with the same gascontained with the gas-retaining object. For example, the dressingsystem 100 may be pre-filled with oxygen and placed within the packagingsystem. By flushing the packaging system 200 with oxygen, the packagingsystem 200 ensures that the dressing system 100 retains the pre-filledoxygen content.

In another embodiment, the packaging system 200 is flushed with adifferent gas than the gas contained with the gas-retaining object. Forexample, the dressing system 100 may contain air that contains othergases in addition to oxygen and may be placed within the packagingsystem 200. By flushing the packaging system 200 with pure oxygen, thepackaging system 200 diffuses the dressing system 100 with additionaloxygen until the gas within the packaging system 200 and the gas withinthe dressing system 100 have reached an equilibrium.

In Block 430, the packaging system 200 is sealed after placing thegas-retaining object within the packaging system 200 and flushing thepackaging system 200 with a gas.

In Block 440, if the gas within the gas retaining device and the gaswithin the packaging system 200 differ, then an exchange of gas occursuntil an equilibrium is achieved. For example, by using the aboveexample describing a dressing system 100 that contains air which issealed within the packaging system 200 flushed with pure oxygen, theoxygen diffuses into within the dressing system 100, while nitrogendiffuses out of the dressing system 100 into the package 200 until anequilibrium is achieved between the gas within the dressing system 100and the packaging system 200. In this embodiment, the gas may beexchanged through the permeable film 160 (FIG. 1).

In Block 550, the packaging system 200 may be opened to remove thegas-retaining object. The packaging system 200 may be utilized to storethe gas-retaining object without degrading the gas within thegas-retaining object. In another embodiment, the packaging system 200may be utilized to infuse the gas-retaining object with a gas.

The flow diagram in FIG. 5 illustrates an exemplary process of utilizingthe dressing system 100 according to one embodiment.

In Block 510, the dressing system 100 is removed from a packaging.

In Block 520, the dressing system 100 is adhered to a user. In oneembodiment, the dressing system 100 may cover a wound or broken skin ofthe user. In one embodiment, the dressing system 100 utilizes theadhesive backing 150 to adhere the dressing system 100 to the user.

In Block 530, a seal is formed between the dressing system 100 and theuser. In one embodiment, the adhesive backing 150 forms the seal betweenthe dressing system 100 and the user.

In Block 540, gas is supplied from the dressing system 100 to the user.In one embodiment, the permeable film 160 is positioned over the woundor broken skin of the user and allows the gas from the dressing system100 to be supplied to wound of the user.

In another embodiment, the permeable film 160 may be positioned overintact skin of the user and allows the gas from the dressing system 100to be supplied to the skin of the user. There are numerous practicalapplications in supplying oxygen to intact skin such as treating sun orradiation damaged skin, exfoliated skin, dermabraded skin, or providingnourishment to aged skin. There may be a synergistic effect with topicalagents as well.

In Block 550, the gas within the reservoir 130 of the dressing system100 may be stored until additional gas is supplied to the user throughthe permeable film 160.

Another embodiment of the packaging system comprises any of thepackaging systems described herein and further comprises a septum, whichas defined herein may be a septum, a valve, Luer lock or any resealableopening, through which one or more gases can be introduced into thepackaging system, then resealed to prevent gases from escaping. Thepackaging system may be charged with the one or more gases in thedesired ratio on site (e.g., hospital, doctor's office).

In another embodiment, the adhesive layer may comprise a gel. The gelmay have semi-adhesive properties, such that the same dressing systemcan be removed and replaced repeatedly. Examples of gels that may beused are described in U.S. Pat. Nos. 4,839,345, 5,354,790 and 5,583,114.

The foregoing descriptions of specific embodiments of the invention havebeen presented for purposes of illustration and description

They are not intended to be exhaustive or to limit the invention to theprecise embodiments disclosed, and naturally many modifications andvariations are possible in light of the above teaching. The embodimentswere chosen and described in order to explain the principles of theinvention and its practical application, to thereby enable othersskilled in the art to best utilize the invention and various embodimentswith various modifications as are suited to the particular usecontemplated.

FIG. 6 illustrates a pouch system 600. The pouch system 600 isconfigured to emit gas into a local environment, similar to the gasemitting pouch system 300. The pouch system 600 includes a first layer610 and a second layer 630. The first layer 610 and the second layer 630may be permeable to gases. In one embodiment, the first layer 610 andthe second layer 630 are bonded through an intermediate layer 620. Theintermediate layer 620 provides the pouch system 600 a more resilientand durable seal between the first layer 610 and the second layer 630 bydiverting the load so that more robust shear force is applied to ahigher bond strength seal rather than strictly a design that puts allthe internal pressure and load on a peel strength surface. By adding theintermediate layer 620 with a narrower diameter than the first layer610, the seal between the first layer 610 and the second layer 630 isreinforced.

The present invention is useful for wound healing for human and animalpatients, for use in laboratories, and anywhere a specific gas orcombination of gases is required to reach a specific, discrete site.

The foregoing descriptions of specific embodiments of the invention havebeen presented for purposes of illustration and description. They arenot intended to be exhaustive or to limit the invention to the preciseembodiments disclosed, and naturally many modifications and variationsare possible in light of the above teaching. The embodiments were chosenand described in order to explain the principles of the invention andits practical application, to thereby enable others skilled in the artto best utilize the invention and various embodiments with variousmodifications as are suited to the particular use contemplated.

REFERENCES

-   1. Whitney J D, “Physiological Effects of Tissue Oxygenation on    Wound”, Heart & Lung, Vol. 18., No. 5, pp. 466-474, September 1989.-   2. Gruber R P, et al., “Skin Permeability to Oxygen and Hyperbaric    Oxygen”, ARCH. SURG., Vol. 101, pp. 69-70, July 1970.-   3. Eaglstein W H, “Experiences with Biosynthetic Dressings”, J. AmM.    Acad. Dermatol., Vol. 12 (2 Pt 2), pp. 434-40, February 1985.-   4. Niinikoski J, et al., “Combination of Hyperbaric Oxygen, Surgery,    and Antibiotics in the Treatment of Clostridial Gas Gangrene”,    Infections in Surgery, pp. 23-37, January 1983.-   5. Fischer B H, “Treatment of Ulcers on the Legs with Hyperbaric    Oxygen”, J. Derm. Surg., Vol. 1, No. 3, pp. 55-58, October 1975.-   6. Heng M, et al., “A Simplified Hyperbaric Oxygen Technique for Leg    Ulcers”, Arch Dermatol, Vol. 120, pp. 640-645, May 1984.-   7. Olejniczak S, et al., “Topical Oxygen Promotes Healing of Leg    Ulcers”, Medical Times, Vol. 104, No. 12, pp. 114-121, December    1976.-   8. Transcript of United States Food & Drug Administration, Center    for Drug Evaluation & Research, Dermatologic and Ophthalmic Drugs    Advisory Committee, 46^(th) Meeting, pp. 15-28, July 14, 1997    (http://www.fda.gov/ohrms/dockets/ac/97/transcpt/3308t1.pdf).-   9. Zhao L L, Davidson J D, Wee S C, Roth S, Mustoe T A, “Effect of    Hyperbaric Oxygen and Growth Factors on Rabbit Ear Ischemic Ulcers,”    Arch Surg/Vol. 129, October 1994.-   10. Winter G D, Perins D J D, Proceedings of the 4^(th) Intl    Congress on Hyperbaric Medicine, Igaku Shoin Ltd, p. 363, 1970.-   11. Silver I A, in Wound Healing & Wound Infection, ed. Hunt T K,    Appleton-Century-Crofts, NY, p 26, 1980.-   12. Prockop D J, et al., “Oxygen-18 studies on the conversion of    proline to collagen hydroxyproline”, Arch Biochem BioPhys V101, p.    499, 1963.-   13. Winter G D., Advances in Exp Med and Bio, V94, p. 673-8, Jul. 4,    1977.-   14. Silver I A, in Epidermal Wound Healing, ed. Maibach H & Rovee D,    Year Book Medical Publishers, Inc, Chicago, p. 291-305, 1972.-   15. Kaufman T, et al., Surgical Forum V34, pp. 111-113, 1983.-   16. Niinikoski J, Clin Plast. Surg, V4, p. 361, 1977.-   17. Kaufman T, et al., Burns, V9, pp. 169-173, 1983.-   18. Utkina O T, Biol. Abstr., V45, 6289, 1964.-   19. Brody A L, Food Technology, Vol. 55, No. 9, pp. 104-106,    September 2001.-   20. Hoogenwerf S W, et al., Letters in Applied Microbiology, Vol.    35, Issue 5, p. 419, November 2002.-   21. Devlieghere F, et al., “Modified atmosphere packaging: state of    the art”, http://www.ifis.co.uk/hottopics/MAParticle2.PDF, September    2000.-   22. Labell, “Controlled & Modified Atmosphere Packaging”, Food    Processing, p. 152, January 1985.-   23. “Biobased Packaging Materials for the Food Industry”, ed. C J    Weber, http://www.nf-2000.org/publications/f4046fin.pdf, November    2000.

1.-56. (canceled)
 57. A method of delivering one or more gases to atarget area comprising: providing an apparatus for supplying one or moregases to a target area, the apparatus comprising: a reservoir; apermeable material in communication with the reservoir which allows oneor more gases contained within the reservoir to communicatetherethrough; and one or more predetermined gases at concentrationsgreater than atmospheric contained within the reservoir, wherein thetissue dressing apparatus does not generate gas and is packaged prior touse with the one or more predetermined gases; and applying to the targetarea the apparatus to delivery the one or more predetermined gasesthrough the permeable material to the target area.
 58. A method ofcharging an apparatus with one or more predetermined gases, comprising:providing an apparatus for supplying one or more gases to a target area,the apparatus comprising: a reservoir; a permeable material incommunication with the reservoir which allows one or more gases tocommunicate therethrough, wherein the tissue dressing apparatus does notgenerate gas; placing the apparatus within a substantiallygas-impermeable container; flushing the container with one or more gasessufficient to produce a desired ratio of gases, wherein at least one ofthe one or more gases is at a concentration greater than atmostpheric;and sealing the container and allowing said gases to permeate thereservoir of said apparatus via the permeable material such that the oneor more gases in the reservoir of the apparatus and the container reachequilibrium.
 59. A method of charging an apparatus with one or moregases, comprising: providing an apparatus for supplying one or moregases to a target area, the apparatus comprising: a reservoir; apermeable material in communication with the reservoir which allows oneor more gases to communicate therethrough, wherein the tissue dressingapparatus does not generate gas; placing the apparatus within asubstantially gas-impermeable container, wherein the apparatus containsone or more gases in a desired ratio within the reservoir, and whereinat least one of the one or more gases is at a concentration greater thanatmospheric; flushing the container with one or more gases in the samedesired ratio; and sealing the container to maintain the desired ratio.60. A method of charging an apparatus with one or more gases,comprising: providing an apparatus for supplying one or more gases to atarget area, the apparatus comprising: a reservoir; a permeable materialin communication with the reservoir which allows one or more gases tocommunicate therethrough, wherein the tissue dressing apparatus does notgenerate gas; placing the apparatus within a substantiallygas-impermeable container wherein the container comprises a septum;sealing the container; connecting a gas source to the septum; flushingthe container with one or more gases sufficient to produce a desiredratio of gases, wherein at least one of the one or more gases is atconcentrations greater than atmospheric; and allowing said gases topermeate the reservoir of said apparatus via the bottom layer such thatthe one or more gases reach equilibrium in the apparatus and thecontainer.
 61. A method of charging an apparatus with one or more gases,comprising: providing an apparatus for supplying one or more gases to atarget area, the apparatus comprising: a reservoir; a permeable materialin communication with the reservoir which allows one or more gases tocommunicate therethrough, wherein the tissue dressing apparatus does notgenerate gas; placing the apparatus within a substantiallygas-impermeable container, wherein both the apparatus and the containerare in a controlled environment having the desired ratio of gases,wherein at least one of the gases of the ratio of gases is at aconcentration greater than atmospheric; sealing the container in thecontrolled environment to capture the desired ratio of gases in thecontainer; and allowing said gases to permeate the reservoir of saidapparatus via the bottom layer such that the desired ratio gases arecontained in the apparatus.
 62. A kit comprising: at least one apparatusfor supplying one or more gases to a target area, wherein at least oneof the one or more gases is at concentrations greater than atmospheric,the apparatus comprising: a reservoir; a permeable material incommunication with the reservoir which allows one or more gasescontained within the reservoir to communicate therethrough, wherein thetissue dressing apparatus does not generate gas; and instructionalmaterial which describes application of the apparatus to a target areato effect delivery of the one or more gases to the target area.